Styrene-isobutylene copolymers and medical devices containing the same

ABSTRACT

In accordance with various aspects of the invention, copolymers comprising styrene and isobutylene monomers are used in the construction of implantable and insertable medical devices for electrical stimulation, including, for example, electronic signal generating components and electrical leads for such devices.

STATEMENT OF RELATED APPLICATION

This application claims priority from U.S. provisional application61/099,064 filed Sep. 22, 2008, which is incorporated herein byreference in its entirety.

FIELD OF THE INVENTION

The present invention relates to styrene-isobutylene copolymers and tomedical devices containing the same.

BACKGROUND OF THE INVENTION

The use of polymeric materials in medical devices for implantation orinsertion into the body of a patient is common in the practice of modernmedicine. For example, polymeric materials such as silicone rubber,polyurethane, and fluoropolymers, for instance, polytetrafluoroethylene(PTFE), expanded PTFE (ePTFE) and ethylene tetrafluoroethylene (ETFE),are used as coating materials/insulation for medical leads, providingmechanical protection, electrical insulation, or both.

As another example, drug eluting stents are known which have polymericcoatings over the stent that release a drug to counteract the effects ofin-stent restenosis. Specific examples of drug eluting coronary stentsinclude commercially available stents from Boston Scientific Corp.(TAXUS, PROMUS), Johnson & Johnson (CYPHER), and others. See S. V.Ranade et al., Acta Biomater. 2005 January; 1(1): 137-44 and R. Virmaniet al., Circulation 2004 Feb. 17, 109(6): 701-5. Various types ofpolymeric materials have been used in such polymeric coatings including,for example, homopolymers such as poly(n-butyl methacrylate) andcopolymers such as poly(ethylene-co-vinyl acetate), poly(vinylidenefluoride-co-hexafluoropropylene), andpoly(styrene-b-isobutylene-b-styrene) triblock copolymers (SIBS). SIBStriblock copolymers have a soft, elastomeric low glass transitiontemperature (Tg) midblock and hard elevated Tg endblocks. Consequently,SIBS copolymers are thermoplastic elastomers, in other words,elastomeric (i.e., reversibly deformable) polymers that form physicalcrosslinks which can be reversed by melting the polymer (or, in the caseof SIBS, by dissolving the polymer in a suitable solvent). SIBS is alsohighly biocompatible and biostable.

SUMMARY OF THE INVENTION

In accordance with various aspects of the invention, copolymerscomprising styrene and isobutylene monomers are used in the constructionof implantable and insertable medical devices for electricalstimulation, including, for example, electronic signal generatingcomponents and electrical leads for such devices.

Potential advantages of the present invention include one or more of thefollowing, among others: (a) enhanced device reliability due to reducedinsulator degradation and/or increased durability; (b) improved speed ofmanufacturing; (c) improved production yield; and (d) reduced lead size.

These and other aspects, embodiments and advantages of the presentinvention will become readily apparent to those of ordinary skill in theart upon review of the Detailed Description and Claims to follow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a schematic longitudinal cross sectional view of a portion ofa medical lead, in accordance with an embodiment of the invention.

FIGS. 1B and 1C are alternative expanded views of area A from FIG. 1A,in accordance with two embodiments of the invention.

FIG. 2A is a schematic longitudinal cross sectional view of a portion ofa medical lead, in accordance with another embodiment of the invention.

FIG. 2B is a cross section of the device of FIG. 2A, taken along lineB-B.

FIG. 3A is a schematic longitudinal cross sectional view of a portion ofa medical lead, in accordance with another embodiment of the invention.

FIG. 3B is a cross section of the device of FIG. 3A, taken along lineB-B.

FIG. 4 is an alternative cross section to that of FIG. 3B.

FIG. 5 is a schematic longitudinal cross sectional view of a portion ofa medical lead, in accordance with yet another embodiment of theinvention.

FIG. 6 is a schematic illustration of an implantable cardiac deviceincluding a lead assembly shown implanted in a sectional view of aheart, the lead assembly employing styrene-isobutylene copolymers inaccordance with an embodiment of the present invention

DETAILED DESCRIPTION OF THE INVENTION

A more complete understanding of the present invention is available byreference to the following detailed description of numerous aspects andembodiments of the invention. The detailed description of the inventionwhich follows is intended to illustrate but not limit the invention.

As is well known, “polymers” are molecules containing multiple copies(e.g., from 2 to 5 to 10 to 25 to 50 to 100 to 1000 to 10,000 or morecopies) of one or more constitutional units, commonly referred to asmonomers. As used herein, the term “monomer” may refer to free monomersand to those that have been incorporated into polymers, with thedistinction being clear from the context in which the term is used.

Polymers may take on a number of configurations, which may be selected,for example, from linear, cyclic and branched configurations, amongothers. Branched configurations include star-shaped configurations(e.g., configurations in which three or more chains emanate from asingle branch point), comb configurations (e.g., configurations having amain chain and a plurality of side chains, also referred to as “graft”configurations), dendritic configurations (e.g., arborescent andhyperbranched polymers), and so forth.

As used herein, “homopolymers” are polymers that contain multiple copiesof a single constitutional unit (i.e., monomer). “Copolymers” arepolymers that contain multiple copies of at least two dissimilarconstitutional units.

As used herein, “block copolymers” are copolymers that contain two ormore polymer blocks that differ in composition, for instance, because aconstitutional unit (i.e., a monomer) is found in one polymer block thatis not found in another polymer block. As used herein, a “polymer block”or “block” is a grouping of constitutional units (e.g., 2 to 5 to 10 to25 to 50 to 100 to 1000 to 10,000 or more units). Blocks can beunbranched or branched. As used herein, a “chain” is a linear(unbranched) block.

In accordance with various aspects of the invention, copolymerscomprising styrene and isobutylene monomers (referred to herein as“styrene/isobutylene copolymers” or “SIBC's”), includingpoly(styrene-co-isobutylene) copolymers and block copolymers comprisingone or more polystyrene blocks and one or more polyisobutylene blocks,for example, poly(styrene-b-isobutylene) diblock copolymers,poly(styrene-b-isobutylene-b-styrene) triblock copolymers (SIBS),poly(isobutylene-b-styrene-b-isobutylene) triblock copolymers (IBSIB),as well as thermoplastic polyurethanes containing polystyrene andpolyisobutylene blocks, among many other possibilities, are used in theconstruction of implantable and insertable medical devices.

More particularly, SIBC containing materials may be used in theconstruction of implantable and insertable medical devices forelectrical stimulation, in accordance with various embodiments of theinvention. Such devices typically include (a) an electronic signalgenerating component and (b) one or more leads. The electronic signalgenerating component commonly contains a source of electrical power(e.g., a sealed battery) and an electronic circuitry package, whichproduces electrical signals that are sent into the body (e.g., theheart, nervous system, etc.). Many electronic signal generatingcomponents also have the capability to receive and respond to signalsthat are emitted by the body (i.e., they are electronic signalgenerating/sensing components). Leads comprise at least one flexibleelongated conductive member (e.g., a wire, cable, etc.), which isinsulated along at least a portion of its length. The conductive memberis adapted to place the electronic signal generating component of thedevice in electrical communication with one or more electrodes, whichprovide for electrical connection with the body. Leads are thus able toconduct electrical signals to the body from the electronic signalgenerating component. Leads may also relay signals from the body to theelectronic signal generating component.

As a specific example, referring to FIG. 6, there is shown a patientinternal medical device (PIMD) that represents one of several types ofdevices with electronic signal generating components and implantableleads that may benefit from the use of SIBC containing materials inaccordance with various embodiments of the present invention. Forexample, the PIMD illustrated in FIG. 6 as a pacemaker/defibrillator,may be representative of all or part of a pacemaker, defibrillator,cardioverter, cardiac monitor, or resynchronization device (e.g.,multichamber or multisite device). Accordingly, the present inventionmay be useful for signal generating components and leads used in a widevariety of implantable medical devices that sense and stimulate cardiacactivity.

The implantable device illustrated in FIG. 6 is an embodiment of thePIMD including an electronic signal generating/sensing component 400(specifically, an implantable pacemaker/defibrillator) electrically andphysically coupled to an intracardiac lead system 402. The intracardiaclead system 402 is implanted in a human body with portions of theintracardiac lead system 402 inserted into a heart 401. Electrodes ofthe intracardiac lead system 402 may be used to detect and analyzecardiac signals produced by the heart 401 and to provide stimulationand/or therapy energy to the heart 401 under predetermined conditions,to treat cardiac arrhythmias of the heart 401.

The PIMD depicted in FIG. 6 is a multi-chamber device, capable ofsensing signals from one or more of the right and left atria 420, 422and the right and left ventricles 418, 424 of the heart 401 andproviding pacing pulses to one or more of the right and left atria 420,422 and the right and left ventricles 418, 424. Low energy pacing pulsesmay be delivered to the heart 401 to regulate the heartbeat or maintaina cardiac rhythm, for example. In a configuration that includescardioversion/defibrillation capabilities, high-energy pulses may alsobe delivered to the heart 401 if an arrhythmia is detected that requirescardioversion or defibrillation.

The intracardiac lead system 402 includes a right ventricular leadsystem 404, a right atrial lead system 405, and a leftatrial/ventricular lead system 406. The right ventricular lead system404 includes an RV-tip pace/sense electrode 412, an RV-coil electrode414, and one or more impedance sense/drive electrodes 461, 462, 463. Inone arrangement, impedance sense and drive electrodes 461, 462, 463 areconfigured as ring electrodes. The impedance drive electrode 461 may belocated, for example, in the right ventricle 418. The impedance senseelectrode 462 may be located in the right atrium 420. Alternatively oradditionally, an impedance sense electrode 463 may be located in thesuperior right atrium 420 or near the right atrium 420 within thesuperior vena cava. The RV-tip electrode 412 is positioned at anappropriate location within the right ventricle 418 for pacing the rightventricle 418 and sensing cardiac activity in the right ventricle 418.The right ventricular lead system may also include one or moredefibrillation electrodes, i.e., coils 414, 416, positioned, forexample, in the right ventricle 418 and the superior vena cava,respectively.

The atrial lead system 405 includes A-tip and A-ring cardiac pace/senseelectrodes 456, 454. In the configuration of FIG. 6, the intracardiaclead system 402 is positioned within the heart 401, with a portion ofthe atrial lead system 405 extending into the right atrium 420. TheA-tip and A-ring electrodes 456, 454 are positioned at an appropriatelocation within the right atrium 420 for pacing the right atrium 420 andsensing cardiac activity in the right atrium 420.

The lead system 402 illustrated in FIG. 6 also includes a leftatrial/left ventricular lead system 406. The left atrial/leftventricular lead system 406 may include, one or more electrodes 434,436, 417, 413 positioned within a coronary vein 465 of the heart 401.The left atrial/left ventricular lead system 406 may include, forexample, one or more endocardial pace/sense leads that are advancedthrough the superior vena cava (SVC), the right atrium 420, the valve ofthe coronary sinus, and the coronary sinus 450 to locate the LA-tip 436,LA-ring 434, LV-tip 413 and LV-ring 417 electrodes at appropriatelocations adjacent to the left atrium 422 and left ventricle 424,respectively. In one configuration, the left atrial/left ventricularlead system 406 is implemented as a single-pass lead. It is understoodthat the preceding descriptions with regard to LV-tip 413 and LV-ring417 electrodes are equally applicable to a lead configuration employingdistal and proximal LV ring electrodes (with no LV-tip electrode).

Additional configurations of sensing, pacing and defibrillationelectrodes may be included in the intracardiac lead system 402 to allowfor various sensing, pacing, and defibrillation capabilities of multipleheart chambers. In other configurations, the intracardiac lead system402 may have only a single lead with electrodes positioned, for example,in the right atrium or the right ventricle to implement single chambercardiac pacing. In yet other embodiments, the intracardiac lead system402 may not include the left atrial/left ventricular lead 406 and maysupport pacing and sensing of the right atrium and right ventricle only.For further information regarding lead configurations, see, e.g., U.S.Pat. No. 7,347,751 to Sweeny et al.

Various lead and electrode arrangements and configurations in additionto the foregoing are clearly within the scope of the devices of thepresent invention.

As can be seen from the foregoing discussion, the present invention isapplicable to a wide variety of medical devices with electronic signalgenerating components and implantable leads. For example, in accordancewith the present invention, SIBC containing materials may be used toform lead insulation components through which at least one conductorextends, including single-lumen and multi-lumen extrusions and tubular(tube-shaped) insulation layers, as well as lead tip materials, headers,and various other lead components. SIBC containing materials may also beused as encapsulation/insulation materials for electronic signalgenerating/sensing components, examples of which include implantablepulse generators, implantable cardioverter-defibrillators (ICDs) andimplantable cardiac resynchronization therapy (CRT) devices. Suchelectronic signal generating/sensing components may be used, forexample, in conjunction with right ventricular lead systems, rightatrial lead systems, and left atrial/ventricular lead systems and may beused to treat, for example, bradycardia, tachycardia (e.g., ventriculartachycardia) or cardiac dyssynchrony in a vertebrate subject (includinghumans, pets and livestock). The present invention is also applicable toleads and electronic signal generating/sensing components forneurostimulation systems such as spinal cord stimulation (SCS) systems,deep brain stimulation (DBS) systems, peripheral nerve stimulation (PNS)systems, gastric nerve stimulation systems, cochlear implant systems,and retinal implant systems, among others.

SIBC's may be synthesized according to known methods, particularlycontrolled/“living” cationic polymerization. For further informationregarding synthesis of styrene-isobutylene copolymers, includingpoly(styrene-b-isobutylene-b-styrene) triblock copolymers (SIBS), see,e.g., U.S. Pat. No. 6,545,097 to Pinchuk et al. and the references citedtherein.

The properties of SIBC's, including SIBS, may be modified by varying theratio of styrene to isobutylene within the copolymer. Typically, thestyrene monomer content of the styrene/isobutylene copolymers of theinvention ranges from 15 to 50 mol % (e.g., from 15 to 17.5 to 20 to22.5 to 25 to 30 to 35 to 40 to 45 to 50 mol %). Thus, where noadditional monomer is provided within the copolymer, the isobutylenecontent of the copolymers typically ranges from 85 to 50 mol % (e.g.,from 85 to 82.5 to 80 to 77.5 to 75 to 70 to 65 to 60 to 55 to 50 mol%).

In various embodiments, the styrene content will be 20 mol % or greater,and more typically 22.5 mol % or greater. This amount of styrene isgreater than the amount that is typically found in the SIBS used instent coatings (i.e., about 17 mol % styrene), which coatings aretypically formed on metallic stents via solution coating processes. Thehigher styrene content is desirable from the perspective of the presentinvention, for example, because it is more readily processed usingthermoplastic techniques such as extrusion and because SIBS with higherstyrene content is stiffer, and thus more torqueable, than low styrenecontent SIBS. Torqueability is frequently a desirable feature forvarious devices that are inserted into a subject by a physician,including electronic leads. As noted above, electronic leads commonlyinclude lead insulation components through which at least one conductorextends, including single-lumen and multi-lumen extrusions and tubularinsulation layers. By selecting stiffer materials for such insulationcomponents, the overall torqueability of the device may be improved.

In certain embodiments, SIBC's, including SIBS, having a relatively highstyrene content (i.e., from 15 to 17 to 19 to 21 mol %) are blended withSIBC's having a relatively low styrene content (i.e., from 22 to 25 to30 to 35 to 40 to 45 to 50 mol %) to provide, for example, a desireddegree of stiffness and/or processability. For example, SIBS having arelatively high styrene content can be thermally extruded with SIBShaving a relatively low styrene content. In some embodiments, the highand low content SIBS are combined in a pre-blending step (e.g., extrudedinto the form of pellets, etc.) prior to extrusion into a final devicecomponent (e.g., a single-lumen or multi-lumen extrusion, etc.)

Thermoplastic elastomers (TPE's) other than SIBC's (referred to hereinas “non-SIBC TPE's”) are also used in certain embodiments of theinvention. These TPE's include thermoplastic polyurethanes (TPU's), forexample, polyether TPU's such as the Pellethane™ family ofpolyether-polyurethanes from Dow Plastics, a business unit of the DowChemical Company. Such polymers can assist in providing thetorqueability that is desired for lead materials, particularly those TPUmaterials with higher isocyanate content, which leads to higherstiffness/modulus. By employing materials with higher stiffness/modulus,thinner material layers may be employed without sacrificingtorqueability, allowing the size of various medical device components,including leads, to be reduced.

In addition to polyether TPU's, non-SIBC TPE's further includepolycarbonate TPU's, polysiloxane TPU's, TPE's based on alkyl acrylatesand/or alkyl methacrylates such as poly(methyl methacrylate-b-n-butylacrylate-b-methyl methacrylate), and TPE's that comprise polyethyleneterephthalate segments and fluorinated segments such as PTFE, ETFE, andhexafluoropropylethylene (HFP) segments, among many others.

Various TPE's, including TPU's such as those described above, however,can eventually exhibit environmental stress cracking upon insertion intoa patient's body, due to the harsh (e.g., oxidative) conditions that areencountered there. Where such TPE's are employed as lead insulationmaterials, such cracking can cause a breach in the insulation thatallows bodily fluids to enter the lead and form shorts, for example,between the conductor(s) and/or the electronic components that generatecurrent through the conductor(s).

SIBC's, including SIBS, on the other hand, possess exceptionalbiostability and biocompatibility. Thus in certain embodiments of theinvention, a SIBC containing material is provided over a non-SIBC TPEcontaining material such as a TPU containing material (which mayprovide, for example, desirable mechanical attributes) in order toprotect the non-SIBC TPE material from the external environment.

Moreover, slow corrosion of the metal conductor(s) within electricalleads is often encountered in the in vivo environment. The metal ionsthus generated from the slow corrosion process are known to react withvarious TPE insulation materials, including TPU's, causing metal ionoxidation (MIO) that can result in degradation and deterioration of thematerial. This can lead to rapid battery depletion and affect theability of the device to reliably provide therapy. A chemically stablematerial could act as an excellent barrier in preventing the migrationof these detrimental metal ions to the TPE insulation material. In someembodiments of the invention, a SIBC containing material is thusprovided between the conductor and a non-SIBC TPE containing material,to protect the non-SIBC TPE containing material from MIO.

Based on the above and other rationales, in various embodiments of theinvention, leads are formed from multiple materials, and in particularare formed from at least one SIBC containing material and at least onenon-SIBC TPE containing material (e.g., a TPU containing material,etc.). Examples include leads that comprise the following among others:(a) a SIBC containing material disposed over a non-SIBC TPE containingmaterial (e.g., to protect the non-SIBC TPE containing material from thesurrounding environment), (b) a SIBC containing material disposed undera non-SIBC TPE containing material (e.g., to protect the non-SIBC TPEcontaining material from MIO due to an underlying conductor), (c) a SIBCcontaining material disposed over a non-SIBC TPE containing materialwhich is disposed over a SIBC containing material (e.g., to protect thenon-SIBC TPE containing material from the surrounding environment andfrom MIO due to an underlying conductor).

In a further embodiment, a non-SIBC TPE containing material is disposedover a SIBC containing material which is disposed over a non-SIBC TPEcontaining material.

In various embodiments, the polymer containing materials that areemployed in the present invention, including SIBC containing materialsand non-SIBC TPE containing materials, are blended or otherwise combinedwith one or more optional supplemental agents as described in moredetail below.

Various specific embodiments of the invention will now be described withfurther reference to the drawings. FIG. 1A is a schematic longitudinalcross sectional view of an insulated (non-electrode) portion of amedical lead 100 in accordance with the invention (which may correspond,for example, to an insulated portion of one of the leads shown in FIG.6, among many other possibilities). The portion of the lead shownincludes a first coiled conductor 130 and a second coiled conductor 132disposed in a co-radial arrangement with one another. An advantage of acoiled configuration for the conductors 130, 132 is that the varioustypes of movements experienced by the lead in vivo are converted intotorsion, which the metals that are typically used to form the coils canreadily tolerate. The coiled conductors 130, 132 may be made, forexample, of stainless steel, Eigiloy, or MP35N, among other suitableconductive materials. The coiled conductors 130, 132 may each beprovided with a layer of insulating material, for example, alow-friction polymeric material such as polytetrafluoroethylene (PTFE)or ethylene-tetrafluoroethylene fluoropolymer (ETFE), among otherlow-friction fluoropolymers and non-fluoropolymers.

The coiled conductors 130,132 are disposed within a tubular insulationlayer 120, which acts to chemically, mechanically and electricallyinsulate the coiled conductors from the external environment and canalso provide the lead with desirable mechanical characteristics such astorqueability.

The tubular insulation layer 120 may comprise a single material, forexample a SIBC containing material. As discussed in more detail below,SIBC containing material for use in the invention may comprise, inaddition to one or more SIBC's (e.g., SIBS, etc.), one or more optionalsupplemental agents, for example, selected from processing aids,blending polymers, particulate agents and therapeutic agents, amongothers. Such a tubular insulation layer 120 may be, for example, solventcoated over the coiled conductors 130,132, extruded over the coiledconductors 130,132, or first extruded and then inserted over the coiledconductors 130,132, among other possibilities. In the latter case, thepre-formed tubular insulation layer 120 may be bonded to the insulatingmaterial on the coiled conductors 130, 132, for example, by a suitableelevated temperature process such as laser bonding (where the insulatingmaterial is a thermoplastic material).

The tubular insulation layer 120 may also comprise two or more materialregions, for example, two or more layers of material, which may form twoor more coaxial tubular material regions.

For example, FIG. 1B is an expanded view of area “A” of FIG. 1A inaccordance with an embodiment of the invention and includes two coaxialtubular material regions 120 a and 120 b of differing composition. Theouter material region 120 a may be, for example, an SIBC containingmaterial such as that previously described. The inner material region120 b may be, for example, a non-SIBC TPE containing material. Asdiscussed in more detail below, non-SIBC TPE containing materials foruse in the invention may comprise, in addition to one or more non-SIBCTPE's (e.g., one or more TPU's, for instance, a polyether polyurethanesuch as Pellethane®, etc.), one or more optional supplemental agents.

The outer material region 120 a may be, for example, solvent coated overthe inner material region 120 b, extruded over the inner material region120 b, co-extruded with the inner material region 120 b, or firstextruded and then inserted over the inner material region 120 b, amongother possibilities. Because the inner and outer material regions 120a,120 b are thermoplastic materials, the outer material region 120 a maybe fused to the inner material region 120 b by a suitable elevatedtemperature process, for instance, a laser bonding process. The use oflaser bonding creates, for instance, the potential for high speedmanufacturing of leads, reduced assembly time and/or improved productionyield.

As another example, FIG. 1C is an expanded view of area “A” of FIG. 1Ain accordance with an alternative embodiment of the invention andincludes three coaxial tubular material regions of differingcomposition. The inner and outer material regions 120 a may be, forexample, an SIBC containing material in accordance with the invention.The intervening region 120 b may be, for example, a non-SIBC TPEcontaining material in accordance with the invention.

Like FIG. 1A, FIG. 5 is a schematic longitudinal cross sectional view ofan insulated portion of a medical lead 100 in accordance with theinvention that includes first and second coiled conductors 130, 132,each of which may be provided with layer of a suitable insulatingmaterial, for example, a fluoropolymer such as those described above,among others.

Unlike FIG. 1A, the first and second coiled conductors 130,132 in FIG. 5are disposed in a co-axial (rather than co-radial) arrangement with oneanother. The inner coiled conductor 132 is provided with a tubularinsulation layer 122, which acts to insulate the coiled conductor 132from the external environment (and from the outer coiled conductor 130as well). The inner tubular insulation layer 122 may also provide thelead with desirable mechanical characteristics such as torqueability.Examples of materials for the inner tubular insulation layer 122include, for example, silicone rubber, PTFE, ETFE or a TPE containingmaterial, for instance, a TPU or a SIBC containing material inaccordance with the invention, among others.

The outer coiled conductor 130 is disposed over the inner tubularinsulation layer 122, and an outer tubular insulation layer 120 isdisposed over the outer coiled conductor 130. Like the tubularinsulation layer of FIG. 1A, the outer tubular insulation layer 120 ofFIG. 5 may be formed of a single material, for example, a SIBCcontaining material. The outer tubular insulation layer 120 of FIG. 5may also comprise two or more material regions, for example, two or morelayers of material, which may form two or more coaxial tubular materialregions. Specific examples of two-material and three-material regionssuitable for use in the outer tubular insulation layer 120 of FIG. 5 aredescribed in conjunction with FIGS. 1B and 1C above.

FIG. 2A is a schematic longitudinal cross sectional view of an insulated(non-electrode) portion 100 a and a non-insulated (electrode) portion100 b of a medical lead 100 in accordance with the invention. Theportion of the lead 100 shown includes a polymer containing innerelongated member 140 (which includes one or more lumens along itslength). Disposed over the right-hand portion 100 b of the innerelongated member 140 is a coiled conductor 130 which may act, forexample, as a shocking/defibrillation electrode for the medical lead100. Because it acts as an electrode, the coiled conductor 130 is eitheruncoated or coated with a conductive layer (e.g., a layer of iridiumoxide, etc.). Disposed over the left-hand portion 100 a of the innerelongated member 140 is a tubular covering 120, which acts to smooth thetransition between the non-electrode portion 100 a and the electrodeportion 100 b (i.e., the tubular covering 120 is provided to create acontinuous diameter for the device). For example, the thickness of thetubular covering 120 can be the same as the diameter of the conductorforming the coil 130, such that the maximum diameter of portion 100 amatches that of portion 100 b. (In addition to ensuring a smooth thetransition between the electrode and non-electrode bearing portions 100b,100 a, the tubular covering 120 can also assist in insulating anyconductor(s) lying within the inner elongated member 140, and mayimprove the mechanical characteristics of the lead, including such astorqueability.) The material for the tubular covering 120 may be, forexample, a TPE containing material (e.g., a TPU or a SIBC containingmaterial, etc.) in accordance with the invention. Such a tubularcovering 120 material may be, for example, solvent coated over the innerelongated member 140, extruded over the inner elongated member 140,co-extruded with the inner elongated member 140, or first extruded andthen inserted over the inner elongated member 140, among otherpossibilities.

FIG. 2B is a cross section of the device of FIG. 2A, taken along lineB-B, and shows a two-lumen inner elongated member 140 with tubularcovering 120. The lumens of the inner elongated member 140 mayaccommodate, for example, a guidewire and a conductor, two conductors,etc. Other configurations, including inner elongated members with one,four, five, six, seven, eight, etc. lumens are also possible. Thematerial for the inner elongated member 140 may be, for example, asilicone containing material or a material containing a TPE such as aTPU or a SIBC such as SIBS, among other possibilities. An advantageassociated with the use of a TPE for the inner elongated member 140 isthat the member 140 can be extruded (a thermoplastic process). Anotheradvantage associated with the use of a TPE for the inner elongatedmember 140 is that the inner elongated member 140 can be inserted intothe tubular covering 120, and the tubular covering 120 can be fused tothe inner elongated member 140 by a suitable elevated temperatureprocess, for instance, a laser bonding process. Such a process may beused, for example, to create a ring shaped thermally fused region 150 asshown in FIG. 2A (e.g., by rotating the device under laser irradiation).By extending the fused region entirely around the circumference ofdevice, an effective seal is formed between the tubular covering 120 andinner elongated member 140. Of course a laser bonding process canproduce thermally fused regions of various shapes in addition to ringshaped regions. For example, the tubular covering 120 can be“spot-fused” to the inner elongated member 140 at various locations (ina process analogous to spot-welding) to prevent unacceptable levels ofmovement between the tubular covering 120 and inner elongated member 140during implantation.

FIG. 3A is a schematic longitudinal cross sectional view of an insulated(non-electrode) portion 100 a and a non-insulated (electrode) portion100 b of a medical lead 100 in accordance with the invention. FIG. 3B isa cross section of the device of FIG. 3A, taken along line B-B. Like thedevice of FIGS. 2A-2B, the device of FIGS. 3A-3B includes apolymer-containing two-lumen inner elongated member 140, a coiledconductor 130, and a tubular covering 120. The device of FIGS. 3A-3B,however, is further provided with an additional tubular covering 122that surrounds the inner elongated member 140. The inner elongatedmember 140 may be formed, for example, from a silicone containingmaterial or a material containing a TPE such as a TPU or a SIBC such asSIBS, among other possibilities. The tubular covering 120 and theadditional tubular covering 122 may be formed, for example, from amaterial containing a TPE such as a TPU or a SIBC such as SIBS, amongother possibilities. In a specific example, both the tubular covering120 and the additional tubular covering 122 are formed from SIBCcontaining materials such as SIBS, such that the inner elongated member140 is covered over its entire length by an SIBC containing material(e.g., to provide environmental protection, etc.).

As above, advantages associated with the use of a TPE for the innerelongated member 140 include the ability to extrude the member 140 andthe ability to fuse an assembly consisting of a previously formed innerelongated member 140, tubular covering 120 and additional tubularcovering 122 using a suitable elevated temperature process, forinstance, a laser bonding process. Such a process may result, forexample, in a ring shaped thermally fused region 150 as shown in FIG.3A.

FIG. 4 is an alternative embodiment of the cross section of FIG. 3Bwhich shows an inner elongated member 140 having three lumens. Otherconfigurations, including inner elongated members with one, four, five,six, seven, eight, etc. lumens are also possible.

In certain embodiments of the invention, the outer insulation layers ofthe devices, including insulation layers formed from SIBC containingmaterials, may be treated to increase their lubricity. For example, theouter insulation layers may be coated with a parylene layer or plasmagrafted with a biocompatible monomer for this purpose, examples of whichinclude hexamethylene disilazane, C₃F₈ (octafluoropropane),trifluoromethane and octafluorocyclobutane, among others.

As noted above, in various embodiments, the polymer containing materialsthat are employed in the present invention, including SIBC containingmaterials and non-SIBC TPE containing materials, may be blended orotherwise combined with one or more optional supplemental agents. Forexample, polymers such as SIBC's and non-SIBC TPE's may be blended withone or more of the following agents, among others: processing aids,blending polymers, particulate agents and therapeutic agents.

Examples of processing aids include, for example, biocompatibleplasticizers, which may be provided in order to enhance theextrudability of the material and may be selected from one or more ofthe following organic plasticizers, among others: dioxane, phthalatederivatives such as dimethyl, diethyl and dibutyl phthalate, glycerol,glycols such as polypropylene, propylene, polyethylene and ethyleneglycol, citrate esters such as tributyl, triethyl, triacetyl, acetyltriethyl, and acetyl tributyl citrates, surfactants such as sodiumdodecyl sulfate and polyoxymethylene (20) sorbitan and polyoxyethylene(20) sorbitan monooleate. Preferred organic plasticizers includepolyethylene glycols (including polyethylene glycols with molecularweights preferably from about 200 to 6,000), dioxane and citrate esters.Citrate esters are renewable resource derivatives derived from citricacid, a tribasic monohydroxy acid (2-hydroxy-1,2,3-propanetricarboxylicacid), C₆H₈O₇, and a natural constituent and common metabolite of plantsand animals. They are non-toxic and have been used as plasticizers witha variety of different polymers.

Examples of blending polymers may be selected from one or more of thefollowing, among others: SIBS with varying styrene and isobutylenecontent, thermoplastic polyurethanes with various hard and soft segmentsincluding those comprising soft segments selected frompolydimethylsiloxane, polyisobutylene, polyether and polycarbonatesegments.

Examples of particulate materials include, for example, organicallymodified silicates. Such agents may act to create a tortuous pathway formoisture thereby decreasing the moisture permeability of the region.Moreover, such agents may maintain the strength and increase the modulusof the material. Supplemental particulate agents further include agentssuch as alumina, silver nanoparticles, silicate/alumina/silvernanoparticle composites, and carbon nanofibers, among others.

In some embodiments, one or more therapeutic agents are included within(e.g., blended with) or attached to (e.g., covalently or non-covalentlybound to) to the polymer containing materials of the invention.Therapeutic agents may be selected, for example, from one or more of thefollowing, among others: blood compatibilizing agents such as heparin,tetraglyme, diamond like carbon, polyethylene glycol, hyaluronic acid,chitosan, methyl cellulose, poly(ethylene oxide), poly(vinylpyrrolidone), phosphorylcholine and Taurine containing monomers, amongothers, prohealing agent such as such as GRGD, YGSIR and GFOGER peptidesand collagen, antithrombotic agents such as sulfated collagen, heparin,albumin and hirudin, steroids such as dexamethasone, as well asphospholipids.

Where a therapeutic agent is present, a wide range of loadings may beused in conjunction with the medical devices of the present invention.Typical therapeutic agent loadings range, for example, from than 1 wt %or less to 2 wt % to 5 wt % to 10 wt % to 25 wt % or more of the polymercontaining materials.

Although various embodiments are specifically illustrated and describedherein, it will be appreciated that modifications and variations of thepresent invention are covered by the above teachings and are within thepurview of the appended claims without departing from the spirit andintended scope of the invention.

1. An implantable and insertable medical device for electrical stimulation comprising: (a) an internal member selected from an elongated conductor and an electronic signal generating component, (b) a first insulating region disposed over the internal member that comprises a thermoplastic polymer other than a copolymer that comprises styrene and isobutylene, (c) a second insulating region disposed over internal member that comprises a copolymer that comprises styrene and isobutylene, wherein at least a portion of the first insulating region is disposed over at least a portion of the second insulating region or wherein at least a portion of the second insulating region is disposed over at least a portion of the first insulating region and (d) an optional third region that comprises a copolymer comprising styrene and isobutylene.
 2. The medical device of claim 1, wherein the internal member is an elongated conductor.
 3. The medical device of claim 1, wherein the first insulating region comprises a thermoplastic polyurethane.
 4. The medical device of claim 1, wherein at least a portion of the second insulating region is disposed over at least a portion of the first insulating region.
 5. The medical device of claim 1, wherein said first region is thermally fused to said second region.
 6. The medical device of claim 5, wherein said first region is fused to said second region via a thermally fused region that is in the shape of a ring.
 7. The medical device of claim 2, wherein the first region corresponds to a multi-lumen extrusion within which the conductor is disposed and the second region corresponds to a tubular insulation layer disposed around the multi-lumen extrusion.
 8. The medical device of claim 7, wherein a coiled electrode is disposed around a first portion of the multi-lumen extrusion and wherein said tubular insulation layer is disposed around a second portion of the multi-lumen extrusion that is adjacent to the first portion.
 9. The medical device of claim 2, wherein the first region corresponds to a first tubular insulation layer disposed around the conductor and the second region corresponds to a second tubular insulation layer disposed around the first tubular insulation layer.
 10. The medical device of claim 1, further comprising said third region that comprises a copolymer comprising styrene and isobutylene.
 11. The medical device of claim 10, wherein the first region is disposed between the second and third regions, within at least a portion of the device.
 12. The medical device of claim 1, wherein said second insulating region comprises a block copolymer that comprises one or more polystyrene blocks and one or more polyisobutylene blocks.
 13. The medical device of claim 1, wherein said second insulating region comprises (a) a copolymer that comprises styrene and isobutylene and (b) a polymer that does not comprise styrene and isobutylene.
 14. The medical device of claim 13, wherein said polymer that does not comprise styrene and isobutylene is selected from a polyurethane that comprises a polyisobutylene soft segment and a polyurethane that comprises a polydimethylsiloxane soft segment.
 15. The implantable and insertable medical device of claim 1, further comprising a therapeutic agent disposed in one or more of the following: the first insulating region, the second insulating region, and the optional third region.
 16. A medical electrical lead comprising: (a) a coiled conductor, said coiled conductor comprising a metallic core and a polymeric coating; (b) a first tubular insulating layer disposed over said coiled conductor, said first tubular insulating layer comprising a copolymer that comprises styrene and isobutylene; (c) an optional second tubular insulating layer; and (d) an optional third tubular insulating layer.
 17. The medical electrical lead of claim 16, wherein the polymeric coating comprises a fluoropolymer.
 18. The medical electrical lead of claim 16, further comprising said second tubular insulating layer disposed over said coiled conductor, said second tubular insulating layer comprising a thermoplastic polymer other than a copolymer that comprises styrene and isobutylene.
 19. The medical electrical lead of claim 18, wherein the second tubular insulating layer is disposed between the coiled conductor and the first tubular insulating layer.
 20. The medical electrical lead of claim 18, further comprising said third tubular insulating layer, said third tubular insulating layer comprising a copolymer comprising styrene and isobutylene.
 21. The medical electrical lead of claim 20, wherein the first tubular insulating layer is disposed over the coiled conductor, wherein the second tubular insulating layer is disposed over the first tubular insulating layer, and wherein the third tubular insulating layer is disposed over the second tubular insulating layer.
 22. The medical device of claim 16, wherein said first tubular insulating layer comprises a block copolymer that comprises one or more polystyrene blocks and one or more polyisobutylene blocks.
 23. The medical device of claim 16, wherein said first tubular insulating layer comprises (a) a copolymer that comprises styrene and isobutylene and (b) a polymer that does not comprise styrene and isobutylene.
 24. The medical device of claim 23, wherein said polymer that does not comprise styrene and isobutylene is selected from a polyurethane that comprises a polyisobutylene soft segment and a polyurethane that comprises a polydimethylsiloxane soft segment.
 25. The medical electrical lead of claim 16, further comprising a therapeutic agent disposed in one or more of the following: the polymeric coating, the first tubular insulating layer, the optional second tubular insulating layer, and the optional third tubular insulating layer.
 26. An implantable and insertable medical device for electrical stimulation comprising: (a) an internal member selected from an elongated conductor and an electronic signal generating component, and (b) a first insulating region disposed over said internal member, wherein said first insulating region comprises first and second copolymers that comprise styrene and isobutylene, wherein the first copolymer has a styrene content that ranges from 15 to 21 mol %, and wherein the second copolymer has a styrene content that ranges from 22 to 50 mol %.
 27. The medical device of claim 26, wherein the internal member is an elongated conductor.
 28. The medical device of claim 26, wherein the internal member is an electronic signal generating component.
 29. The medical device of claim 26, wherein the first and second copolymers are thermally extruded in a pre-blending step prior to thermal extrusion into a single-lumen or multi-lumen device component that provides said first insulating region.
 30. The implantable and insertable medical device of claim 26, further comprising a therapeutic agent disposed in the first insulating region. 